Gregory Kinnear was born in Logansport, Indiana, the son of Suzanne, a homemaker, and Edward Kinnear, a career diplomat who worked for the U.S. State Department. He has two brothers, James and Steven. As a child, the Kinnear family moved around a lot, from Beirut to Athens, part of a group sometimes referred to as the "Foreign Service Brats". While a student at the American Community Schools in Athens, Greg Kinnear first ventured into the role of talk show host with his radio show "School Daze With Greg Kinnear". Returning to the States for a college education, he attended the University of Arizona, where he graduated in 1985 with a degree in broadcast journalism.

From Arizona, Kinnear headed out to Los Angeles, where he landed his first job as a marketing assistant with Empire Entertainment. Following this job he auditioned to be an MTV VJ, but failed and became a host and on-location reporter for Movietime, the precursor to E! Entertainment Television. He also had bit parts on such television shows as L.A. Law and Life Goes On.

Later, he would host a short-lived game show, College Mad House, which was spun-off from the kids' show, Fun House. After that, he would later become the creator, co-executive producer, and host of Best of the Worst which aired from 1990 to 1991. In 1991, Kinnear's third television exposure immensed when he became the first host of Talk Soup until 1995, when he left the show for the NBC late-night talk show, Later with Greg Kinnear (1994).

It was in 1994 that Kinnear had his first big screen role, as a talk show host yet again in the Damon Wayanscomedy Blankman. In 1995 he won the part of David Larrabee in Sydney Pollack's remake of Billy Wilder's 1954 classic Sabrina. He later played the lead role in the 1996 comedy Dear God. In 1997, he was cast in James L. Brooks' comedy-drama, As Good as It Gets, for which he received a nomination for the Academy Award for Best Supporting Actor. His next film, A Smile Like Yours, had him starring opposite Lauren Hollyas part of a couple trying to have a baby. His next film was the popular You've Got Mail, in which he played Meg Ryan's significant other. His following films were Mystery Men, Nurse Betty, Loser, and Someone Like You.

In 2002, Kinnear starred in the movie Auto Focus about the life and murder of actor Bob Crane. In 2003 he starred in Stuck On You, a comedy in which he played a conjoined twin who pursues his dream of becoming a Hollywood actor. In 2005 he starred in the black comedy The Matador opposite Pierce Brosnan.

In 2006, Kinnear co-starred with Steve Carellin the Oscar-winning comedy-drama Little Miss Sunshine, and with Mark Wahlberg in Invincible, based on the true story of a bartender who tries out for the Philadelphia Eagles football team. He also appeared in Fast Food Nation, playing a fast food executive who discovers secrets about his company. In 2008 starred in the movie "Flash of Genius", a docudrama about Robert Kearns who invented the intermittent windshield wiper. In 2010, Kinnear will star as the estranged father of Miley Cyrus' character in The Last Song.

His portrayal of then-Major Bruce P. Crandall in 2002's We Were Soldiers brought public attention to Crandall's heroism during the 1965 Battle of Ia Drang. (On February 26, 2007, Crandall was awarded the Medal of Honor by President Bush for his actions depicted by Kinnear.)